Novel compositions for use in embolizing blood vessels

ABSTRACT

Disclosed are compositions suitable for use in embolizing blood vessels which compositions comprise a polymer, a biocompatible solvent and a contrast agent. The polymer is selected from the group consisting of polyacrylonitrile, polyurethane, polyvinylacetate, cellulose acetate butyrate, nitrocellulose and copolymers of urethane/carbonate and copolymers of styrene/maleic acid.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] This invention is directed to novel compositions suitable for usein embolizing blood vessels. In particular, this invention is directedto embolizing compositions comprising a biocompatible polymer, abiocompatible solvent and a contrasting agent. The compositions of thisinvention find particular utility in embolizing blood vessels in, forexample, the treatment of aneurysms and in ablating diseased tissues.

REFERENCES

[0003] The following publications are cited in this application assuperscript numbers:

[0004]¹ Mandai, et al., “Direct Thrombosis of Aneurysms with CelluloseAcetate Polymer”, J. Neurosurg., 77:497-500 (1992)

[0005]² Kinugasa, et al., “Direct Thrombosis of Aneurysms with CelluloseAcetate Polymer”, J. Neurosurg., 77:501-507 (1992)

[0006]³ Greff, et al., U.S. patent application Ser. No. 08/508,248, for“Cellulose Diacetate Compositions for Use in Embolizing Blood Vessels,filed Jul. 27, 1995.

[0007]⁴ Greff, et al., U.S. patent application Ser. No. 08/507,863, for“Novel Compositions for Use in Embolizing Blood Vessels”, filed Jul. 27,1995.

[0008]⁵ Evans, et al., U.S. patent application Ser. No. ______, for“Methods for the Reversible Sterilization of Male Mammals, filedconcurrently herewith as Attorney Docket No. 018413-007

[0009]⁶ Evans, et al., U.S. patent application Ser. No. ______, for“Methods for the Reversible Sterilization of Female Mammals, filedconcurrently herewith as Attorney Docket No. 018413-014

[0010] All of the above references are herein incorporated by referencein their entirety to the same extent as if each individual reference wasspecifically and individually indicated to be incorporated herein byreference in its entirety.

[0011] 2. State of the Art

[0012] It is desirable in many clinical situations to embolize bloodvessels to prevent/control bleeding (e.g., organ bleeding,gastrointestinal bleeding, vascular bleeding, bleeding associated withan aneurysm) or to ablate diseased tissue (e.g., tumors, etc.).Embolization of blood vessels has heretofore employed certain polymercompositions and particulates, e.g., silicone, metallic coils,sclerosing materials and the like. Because of their ease in delivery,water insoluble non-biodegradable polymers such as celluloseacetate^(1,2,3) or ethylene vinyl alcohol⁴ dissolved in, for example,DMSO have been employed to embolize blood vessels. These compositionsare delivered to the vascular site to be embolized by, for example, acatheter or a syringe. Typically, these compositions will comprise acontrast agent to facilitate guidance of the catheter or syringe to thevascular site as well as the placement of the polymer precipitate whichembolizes the blood vessel. Upon contact with the aqueous bloodenvironment at this vascular site, the DMSO dissipates away from theinsoluble polymer which results in polymer precipitation andembolization of the blood vessel.

[0013] In addition to use in embolizing blood vessels, thesecompositions can also be employed in the reversible sterilization ofmammalian males and females.^(5,6) In the former case, the polymercomposition is injected into the vas deferens and upon contact with theaqueous fluid therein, precipitates to block the vas. In the lattercase, the polymer composition is injected into the fallopian tubes andupon contact with the aqueous fluid therein, precipitates to block thetube. In either case, sterilization arising from the blockage can bereversed at a latter date by injecting DMSO into the polymer blockage toremove the polymer.

[0014] While progress has been made in the development of compositionswhich can be employed in such methods, only a limited number of polymerssuitable for use in such compositions have been identified. While thesepolymers minimally meet the criteria for use in these environments, theidentity of additional polymers is essential to developing versatilemethods utilizing the specific characteristics of each polymer. Forexample, embolization techniques requiring deep vascular penetrationwill require a composition having a relatively slow polymerprecipitation rate. Contrarily, techniques requiring rapid embolizationof, for example, a bleeding aneurysm or a high blood flood vascular sitewill require a composition having a relatively fast polymerprecipitation rate.

[0015] In either case, polymers suitable for use in such compositionsmust meet stringent conditions for use in embolizing blood vessels, inreversible sterilization, etc. Specifically, suitable polymers ideallyshould be soluble in the biocompatible solvent, be easy to deliver(e.g., low viscosity) via a catheter or a syringe, be compatible with acontrast agent, and the resulting precipitate should form a well definedcoherent mass which is non-biodegradable. This last requirement is, ofcourse, essential to use in vivo where a coherent mass is critical toeither successful embolization or sterilization. Likewise, compatibilitywith the contrast agent is necessary in order to permit monitoring thein vivo injection of the composition and to confirm its presence afterthe procedure is complete.

SUMMARY OF THE INVENTION

[0016] This invention is directed to the discovery of novel polymerswhich are suitable in compositions useful in in vivo applications suchas in embolizing blood vessels and/or reversibly sterilizing mammalianpatients. Specifically, this invention is directed to the discovery thatpolymers such as polyacrylonitrile, polyvinylacetate, cellulose acetatebutyrate, nitrocellulose and copolymers of urethane/carbonate andcopolymers of styrene/maleic acid can be employed in combination with abiocompatible solvent and a contrast agent and the resultingcompositions are suitable for use in embolizing blood vessels, inreversible sterilization of mammalian patients, etc.

[0017] Accordingly, in one of its composition aspects, this invention isdirected to a composition comprising:

[0018] (a) from about 2.5 to about 8.0 weight percent of a polymerselected from the group consisting of polyacrylonitrile,polyvinylacetate, cellulose acetate butyrate, nitrocellulose andcopolymers of urethane/carbonate and copolymers of styrene/maleic acid,and mixtures thereof;

[0019] (b) from about 10 to about 40 weight percent of a contrast agent;

[0020] (c) from about 52 to about 87.5 weight percent of a biocompatiblesolvent

[0021] wherein the weight percent of the polymer, contrast agent andbiocompatible solvent is based on the total weight of the completecomposition.

[0022] In one of its method aspects, this invention is directed to amethod for embolizing a blood vessel by injecting into said blood vessela sufficient amount of a composition comprising:

[0023] (a) from about 2.5 to about 8.0 weight percent of a polymerselected from the group consisting of polyacrylonitrile,polyvinylacetate, cellulose acetate butyrate, nitrocellulose andcopolymers of urethane/carbonate and copolymers of styrene/maleic acid,and mixtures thereof;

[0024] (b) from about 10 to about 40 weight percent of a contrast agent;

[0025] (c) from about 52 to about 87.5 weight percent of a biocompatiblesolvent

[0026] wherein the weight percent of the polymer, contrast agent andbiocompatible solvent is based on the total weight of the completecomposition

[0027] under conditions wherein a precipitate is formed which embolizesthe blood vessel.

[0028] In a preferred embodiment, the contrast agent is a waterinsoluble contrast agent. In still a further preferred embodiment, thebiocompatible solvent is dimethylsulfoxide (DMSO).

DETAILED DESCRIPTION OF THE INVENTION

[0029] This invention is directed to novel compositions comprisingspecific polymers, a contrast agent and a biocompatible solvent.

[0030] Prior to discussing this invention in further detail, thefollowing terms will first be defined:

[0031] The term “embolizing” as used in conjunction with “embolizingcompositions” and “embolizing agents” refers to a process wherein amaterial is injected into a blood vessel which thereafter fills or plugsthe blood vessel and/or encourages clot formation so that blood flowthrough the vessel ceases. The embolization of the blood vessel isimportant in preventing/controlling bleeding (e.g., organ bleeding,gastrointestinal bleeding, vascular bleeding, bleeding associated withan aneurysm) or to ablate diseased tissue (e.g., tumors, etc.) bycutting off its blood supply.

[0032] The term “contrast agent” refers to a biocompatible (non-toxic)radiopaque material capable of being monitored during injection into amammalian subject by, for example, radiography. The contrast agent canbe either water soluble or water insoluble. Examples of water solublecontrast agents include metrizamide, iopamidol, iothalamate sodium,iodomide sodium, and meglumine. Examples of water insoluble contrastagents include tantalum, tantalum oxide, and barium sulfate, each ofwhich is commercially available in the proper form for in vivo useincluding a particle size of about 10 μm or less. Other water insolublecontrast agents include gold, tungsten, and platinum powders.

[0033] Preferably, the contrast agent is water insoluble (i.e., has awater solubility of less than 0.01 mg/ml at 20° C.).

[0034] The term “biocompatible solvent” refers to an organic materialliquid at least at body temperature of the male mammal in which thebiocompatible polymer is soluble and, in the amounts used, issubstantially non-toxic. Suitable biocompatible solvents include, by wayof example, dimethylsulfoxide, analogues/homologues ofdimethylsulfoxide, ethanol, acetone, and the like. Aqueous mixtures withthe biocompatible solvent can also be employed provided that the amountof water employed is sufficiently small that the dissolved polymerprecipitates upon contact with the vas deferens fluid. Preferably, thebiocompatible solvent is dimethylsulfoxide.

[0035] The term “encapsulation” as used relative to the contrast agentbeing encapsulated in the precipitate is not meant to infer any physicalentrapment of the contrast agent within the precipitate much as acapsule encapsulates a medicament. Rather, this term is used to meanthat the contrast agent and copolymer form an integral coherentprecipitate which does not separate into a copolymer component and acontrast agent component.

[0036] The term “hydrocarbyl” refers to organic residues comprising onlycarbon and hydrogen atoms which residues include, by way of example,alkyl, aryl, alkylaryl, arylalkyl, alkenyl, etc. The hydrocarbyl grouptypically contains from 1 to 12 carbon atoms.

[0037] Compositions

[0038] The compositions of this invention are prepared by conventionalmethods whereby each of the components is added and the resultingcomposition mixed together until the overall composition issubstantially homogeneous. Specifically, sufficient amounts of theselected polymer are added to the biocompatible solvent to achieve theeffective concentration for the complete composition. Preferably, theembolizing composition will comprise from about 2.5 to about 8.0 weightpercent of the polymer based on the total weight of the composition andmore preferably from about 4 to about 5.2 weight percent. If necessary,gentle heating and stirring can be used to effect dissolution of thepolymer into the biocompatible solvent, e.g., 12 hours at 50° C.

[0039] The polymers suitable for use in this composition include, by wayof example, polyacrylonitrile, polyvinylacetate, cellulose acetatebutyrate, nitrocellulose and copolymers of urethane/carbonate andcopolymers of styrene/maleic acid, and mixtures of such polymers.Copolymers of urethane/carbonate include polycarbonates that are diolterminated which are then reacted with a diisocyanate such as methylenebisphenyl diisocyanate to provide for the urethane/carbonate copolymers.Likewise, copolymers of styrene/maleic acid refer to copolymers having aratio of styrene to maleic acid of from about 7:3 to about 3:7.

[0040] In any event, the polymers typically will have a molecular weightof at least about 50,000 and more preferably from about 75,000 to about300,000. In a particularly preferred embodiment, the molecular weight ofthe polymer can be selected relative to the desired viscosity of theresulting composition. It being understood, of course, that polymers ofhigher molecular weight will provide for a higher viscosity in thecomposition as compared to the same polymer having a lower molecularweight.

[0041] Sufficient amounts of the contrast agent are then added to thebiocompatible solvent to achieve the effective concentration for thecomplete composition. Preferably, the composition will comprise fromabout 10 to about 40 weight percent of the contrast agent and morepreferably from about 20 to about 40 weight percent and even morepreferably 35 weight percent. Insofar as the contrast agent is notsoluble in the biocompatible solvent, stirring is employed to effecthomogeneity of the resulting suspension. In order to enhance formationof the suspension, the particle size of the contrast agent is preferablymaintained at about 10 μm or less and more preferably at from about 1 toabout 5 μm (e.g., an average size of about 2 μm). In one preferredembodiment, the particle size of the contrast agent is prepared, forexample, by fractionation. In such an embodiment, a water insolublecontrast agent such as tantalum having a particle size of less thanabout 20 microns is added to an organic liquid such as ethanol(absolute) preferably in a clean environment. Agitation of the resultingsuspension followed by settling for approximately 40 seconds permits thelarger particles to settle faster. Removal of the upper portion of theorganic liquid followed by separation of the liquid from the particlesresults in a reduction of the particle size which is confirmed under amicroscope. The process is optionally repeated until a desired particlesize is reached.

[0042] The particular order of addition of components to thebiocompatible solvent is not critical and stirring of the resultingsuspension is conducted as necessary to achieve homogeneity of thecomposition. Preferably, mixing/stirring of the composition is conductedunder an anhydrous atmosphere at ambient pressure. The resultingcomposition is heat sterilized and then stored preferably in sealedamber bottles or vials until needed.

[0043] Each of the polymers recited herein is commercially available butcan also be prepared by methods well known in the art. For example,polymers are typically prepared by conventional techniques such asradical, thermal, UV, γ irradiation, or electron beam inducedpolymerization employing, as necessary, a polymerization catalyst orpolymerization initiator to provide for the polymer composition. Thespecific manner of polymerization is not critical and the polymerizationtechniques employed do not form a part of this invention.

[0044] In order to maintain solubility in the biocompatible solvent, thepolymers described herein are preferably not cross-linked.

[0045] Methods

[0046] The compositions described above can then be employed in methodsfor embolizing mammalian blood vessels or for reversible sterilizationof mammalian patients. In the case of blood vessel embolization, asufficient amount of this composition is introduced into the selectedblood vessel by conventional means (e.g., injection or catheter deliveryunder fluoroscopy) so that upon precipitation of the polymer, the bloodvessel is embolized. The particular amount of embolizing compositionemployed is dictated by the total volume of the vasculature to beembolized, the concentration of polymer in the composition, the rate ofprecipitation (solids formation) of the polymer, etc. Such factors arewell within the skill of the art. In the case of the copolymers recitedabove, the rate of precipitation can be controlled by changing theoverall hydrophobicity/hydrophilicity of the polymer with fasterprecipitation rates being achieved by a more hydrophobic polymercomposition. In this regard, increasing the amount of butyrate content(at the expense of the acetate content) in the cellulose acetatebutyrate will also increase the hydrophobicity of the polymer.

[0047] One particularly preferred method for delivering the embolizingcompositions of this invention to the selected vascular site is via asmall diameter medical catheter. The particular catheter employed is notcritical provided that polymeric catheter components are compatible withthe embolizing composition (i.e., the catheter components will notreadily degrade in the embolizing composition). In this regard, it ispreferred to use polyethylene in the catheter components because of itsinertness in the presence of the embolizing composition describedherein. Other materials compatible with the embolizing compositions canbe readily determined by the skilled artisan and include, for example,other polyolefins, fluoropolymers (e.g., Teflon™), silicone, etc.

[0048] When delivered by catheter, the injection rate dictates, in part,the form of the precipitate at the vascular site. Specifically, lowinjection rates of approximately 0.05 to 0.3 cc/minute will provide fora precipitate in the form of a kernel or nodule which is particularlybeneficial for site specific embolization because the precipitate formsprimarily at the point of injection. Contrarily, high injection rates ofabout 0.1 to 0.5 or more cc/several seconds (e.g., up to 10 seconds)will provide for a filament like mass projecting downstream from thecatheter tip which may be particularly beneficial for providing theembolizing agent deep into the vascular tree. Such procedures aresuitable for embolizing tumor masses, organs and arteriovenousmalformations (AVM).

[0049] When introduced into the vascular site, the biocompatible solventdiffuses rapidly into the blood and a solid precipitate forms whichprecipitate is the water insoluble polymer with the contrast agentencapsulated therein. Without being limited to any theory, it isbelieved that initially, a soft gel to spongy solid precipitate formsupon contact with the blood. This precipitate then restricts blood flow,entrapping red cells thereby causing clot embolization of the bloodvessel.

[0050] Utility

[0051] The compositions described herein are useful in embolizingmammalian blood vessels which, in turn, can be used to prevent/controlbleeding (e.g., organ bleeding, gastrointestinal bleeding, vascularbleeding, bleeding associated with an aneurysm) or to ablate diseasedtissue (e.g., tumors, etc.). Accordingly, these compositions find use inhuman and other mammalian subjects requiring embolization of bloodvessels.

[0052] Additionally, these compositions can be used in the reversiblesterilization of mammalian patients as described in concurrently filedapplications by Evans, et al.^(5,6).

[0053] It is contemplated that these compositions can be employed as acarrier for a compatible pharmaceutically active compound wherein thiscompound is delivered in vivo for subsequent release. Such compoundsinclude by way of example only antibiotics, anti-inflammatory agents,chemotherapeutic agents, and the like.

[0054] The following examples are set forth to illustrate the claimedinvention and are not to be construed as a limitation thereof.

EXAMPLES

[0055] Unless otherwise stated, all temperatures are in degrees Celsius.Also, in these examples, unless otherwise defined below, theabbreviations employed have their generally accepted meaning:

[0056] cc=cubic centimeter

[0057] cps=centipoise

[0058] DMSO=dimethylsulfoxide

[0059] gm=gram

[0060] ML=milliliter

[0061] RT=room temperature

Example 1

[0062] The purpose of this example is to determine the suitability ofdifferent polymers in compositions comprising DMSO and a contrast agent.The tests were conducted as follows:

[0063] 1. 1.2 grams of a candidate polymer was weighed out and placedinto a 20 mL bottle that had a Teflon capliner in the lid.

[0064] 2. 12.5 mL (13.8 gm) DMSO was added to the bottle containing thecandidate polymer and the cap was placed onto the vial tightly.

[0065] 3. Each of the bottles was placed in a tightly sealed half gallonjar and placed in an oven at 50° C.

[0066] 4. The bottles were maintained in the oven for approximately 72hours and thereafter were allowed to cool to RT.

[0067] 5. Once the samples reached RT, they were visually examined todetermine if the polymers were soluble in DMSO.

[0068] 6. The viscosity of each of the soluble polymers was thenestimated relative to a 100 cps fluid standard. All viscosities reportedare for 20° C.

[0069] 7. Each of the dissolved polymer solutions was drawn into asyringe and then injected into a physiological saline solution through a20 gauge blunt needle to determine whether a coherent precipitateformed.

[0070] In this example, 21 different polymer compositions were evaluatedand the results are set forth in Table I below. TABLE I CoherentViscosity Polymer Dissolve Precipitate (cps) polymethyl YES YES <100methacrylate (brittle) polybutyl PARTIAL — — methacrylate poly(acrylicacid- NO — — co-maleic acid) Na polyacrylonitrile YES YES >100 (strong)poly(ethylene-co- NO — — methacrylic acid) Na poly(acrylamide- NO — —co-acrylic acid) polycarbonate NO — — poly(carbonate- YES YES ˜100urethane) (rubbery) polyurethane NO — — polyamide NO — — (Nylon 6 or 66)poly(ethylene- PARTIAL — — co-vinyl acetate) polysulfone PARTIAL — —poly(vinylacetate) YES YES <100 (weak) cellulose acetate YES YES <100butryate (weak) polyester NO — — polyester NO — — silicone resin YES NO <50 (flock) nitrocellulose YES YES >100 (weak) poly(styrene- YES YES<100 co-maleic acid) (weak) poly(vinylpyrro- YES NO <100 lidone co-vinyl(liquid) acetate) poly(methyl vinyl YES NO >100 ether-co-maleic acid(liquid)

[0071] The above results indicate that of the 21 polymers tested, only11 were soluble in DMSO and of the 11 only 8 formed precipitates in thesaline solution. Of these 8, the brittleness of the polymethylmethacrylate precludes its use in embolizing compositions. Accordinglyonly 6 of the polymers tested are suitable for use in this invention.These six polymers were as follows: polyacrylonitrile, polyvinylacetate,cellulose acetate butyrate, nitrocellulose and copolymers ofurethane/carbonate and copolymers of styrene/maleic acid. Certainpolymers provide properties which are more advantageous in certainenvironments over others.

Example 3

[0072] The purpose of this example is to illustrate how an in vivoapplication of the methods of this invention in the sterilization of amale mammal could be accomplished. In this example, a 50 pound male dogis prepared for sterilization using a composition comprising 5.8 weightpercent polyacrylonitrile (PAN) and 20 weight percent tantalum in DMSO.This composition is loaded into a syringe having a needle attachedthereto. Local procaine anaesthesia is applied to the scrotum area ofthe subject. The vas deferens of one side is gripped through the skin bya vas-fixation clamp and lifted. The syringe needle is used to puncturethe vas in the direction away from the testis. The PAN polymercomposition (0.3 cc) is then delivered to the lumen of the vas deferens.The delivery is easily visualized with fluoroscopy due to the presenceof a contrast agent in the polymer composition. After delivery, the DMSOin the PAN composition rapidly diffuses and the PAN precipitates in thelumen resulting in a blockage of the vas deferens. After about 5minutes, the polymer is fully precipitated and the syringe needle isremoved from vas.

[0073] The same procedure is repeated with the other vas deferens of themale subject.

Example 4

[0074] The purpose of this example is to illustrate an in vivoembolization using a composition of this invention.

[0075] In this example, a 50 pound male hound was prepared for bloodvessel embolization using a composition comprising 5.8 weight percentpoly(carbonate-urethane), 20 weight percent tantalum in DMSO was loadedinto a syringe. Embolization of the left kidney proceeded by placementof a 3F micro catheter into the kidney through a 5F AngioDynamicsHeadhunter catheter. The catheter was advanced into the renal artery,flushed with contrast agent to identify the location and then flushedwith saline, followed by DMSO, followed by 0.3 cc of the compositiondescribed above. The composition was quickly injected into the renalartery over several seconds. After delivery of about 0.2 cc of thecomposition, the upper pole of the kidney was blocked. Delivery of theremaining composition resulted in the entire kidney being embolized.

[0076] The above results indicate that the compositions of thisinvention are suitable for in vivo embolization of blood vessels inmammalian subjects.

[0077] From the foregoing description, various modifications and changesin the composition and method will occur to those skilled in the art.All such modifications coming within the scope of the appended claimsare intended to be included therein.

What is claimed is:
 1. A composition comprising: (a) from about 2.5 toabout 8.0 weight percent of a polymer selected from the group consistingof polyacrylonitrile, polyvinylacetate, cellulose acetate butyrate,nitrocellulose and copolymers of urethane/carbonate and copolymers ofstyrene/maleic acid, and mixtures thereof; (b) from about 10 to about 40weight percent of a contrast agent; (c) from about 52 to about 87.5weight percent of a biocompatible solvent wherein the weight percent ofthe polymer, contrast agent and biocompatible solvent is based on thetotal weight of the complete composition.
 2. The composition accordingto claim 1 wherein said contrast agent is a water insoluble contrastagent.
 3. The composition according to claim 2 wherein saidbiocompatible solvent is DMSO.
 4. The composition according to claim 2wherein said contrast agent is tantalum.
 5. The composition according toclaim 2 wherein said contrast agent is tantalum oxide.
 6. Thecomposition according to claim 3 wherein said contrast agent is bariumsulfate.
 7. The composition according to claim 1 wherein said polymer ispolyacrylonitrile.
 8. The composition according to claim 1 wherein saidpolymer is polyvinylacetate.
 9. The composition according to claim 1wherein said polymer is cellulose acetate butyrate.
 10. The compositionaccording to claim 1 wherein said polymer is nitrocellulose.
 11. Thecomposition according to claim 1 wherein said polymer is a copolymer ofurethane/carbonate.
 12. The composition according to claim 1 whereinsaid polymer is a copolymer of styrene/maleic acid.
 13. A method forembolizing a blood vessel by injecting into said blood vessel asufficient amount of a composition comprising: (a) from about 2.5 toabout 8.0 weight percent of a polymer selected from the group consistingof polyacrylonitrile, polyvinylacetate, cellulose acetate butyrate,nitrocellulose and copolymers of urethane/carbonate and copolymers ofstyrene/maleic acid, and mixtures thereof; (b) from about 10 to about 40weight percent of a contrast agent; (c) from about 52 to about 87.5weight percent of a biocompatible solvent wherein the weight percent ofthe polymer, contrast agent and biocompatible solvent is based on thetotal weight of the complete composition under conditions wherein aprecipitate is formed which embolizes the blood vessel.
 14. The methodaccording to claim 13 wherein said contrast agent is a water insolublecontrast agent.
 15. The method according to claim 13 wherein saidbiocompatible solvent is DMSO.
 16. The method according to claim 14wherein said contrast agent is tantalum.
 17. The method according toclaim 14 wherein said contrast agent is tantalum oxide.
 18. The methodaccording to claim 14 wherein said contrast agent is barium sulfate. 19.The method according to claim 13 wherein said polymer ispolyacrylonitrile.
 20. The method according to claim 13 wherein saidpolymer is polyvinylacetate.
 21. The method according to claim 13wherein said polymer is cellulose acetate butyrate.
 22. The methodaccording to claim 13 wherein said polymer is nitrocellulose.
 23. Themethod according to claim 13 wherein said polymer is a copolymer ofurethane/carbonate.
 24. The method according to claim 13 wherein saidpolymer is a copolymer of styrene/maleic acid.
 25. The method accordingto claim 13 wherein the embolizing composition is injected into theblood vessel at a rate of about 0.05 to 0.3 cc/minute.
 26. The methodaccording to claim 13 wherein the embolizing composition is injectedinto the blood vessel at a rate of at least 0.6 cc/minute.
 27. Themethod according to claim 26 wherein the injection rate of at least 0.6cc/minute is employed to form a filament like mass projecting downstream from the catheter tip for embolizing tumor masses, organs andarteriovenous malformations (AVM).